In vitro biological evaluation and consideration about structure-activity relationship of silver(I) aminoacidate complexes

J Inorg Biochem. 2020 Sep:210:111170. doi: 10.1016/j.jinorgbio.2020.111170. Epub 2020 Jul 3.

Abstract

Two silver(I) aminoacidate complexes {[Ag4(L-HAla)4(NO3)3]NO3}n (AgAla, complex 1, Ala = alanine) and {[Ag(L-Phe)]}n (AgPhe, complex 2, Phe = phenylalanine) were prepared and characterized by elemental, spectral analysis (FT-IR, NMR techniques) and single crystal X-ray analysis in solid state and their solution stability was measured in biological testing time-scale by 1H NMR. The bridging coordination modes of the zwitterionic Ala and deprotonated Phe ligands led to the formation of 1D polymeric chains of the complexes. The significant argentophilic interactions are presented in the structure of AgAla. Antimicrobial testing of prepared Ag(I) complexes was evaluated by IC50 and MIC values and were compared with AgGly, silver(I) sulfadiazine and AgNO3 samples. Moreover, MTS test was used to the testing of broad range antiproliferative activity of studied compounds against different cancer cell lines and also to the investigation of calf thymus DNA interactions by absorption spectroscopy, fluorescence spectroscopy, Ethidium bromide/Hoechst 33258 displacement experiments and circular dichroism spectroscopy. To evaluate the pUC19 DNA fragmentation by silver(I) complexes, the agarose gel electrophoresis was used. In addition to biological evaluation we used lipophilicity measurement results in the discussion about structure-activity relationship (SAR).

Keywords: Anticancer activity; Antimicrobial activity; Groove binding; Nuclease activity; Silver(I) complexes; Stability in solution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / chemistry
  • Alanine / metabolism
  • Alanine / pharmacology*
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemistry
  • Antifungal Agents / metabolism
  • Antifungal Agents / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Candida parapsilosis / drug effects
  • Catalysis
  • Cattle
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacology*
  • DNA / metabolism
  • DNA Cleavage / drug effects
  • Drug Screening Assays, Antitumor
  • Escherichia coli / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Phenylalanine / chemistry
  • Phenylalanine / metabolism
  • Phenylalanine / pharmacology*
  • Silver / chemistry
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antineoplastic Agents
  • Coordination Complexes
  • Silver
  • Phenylalanine
  • DNA
  • calf thymus DNA
  • Alanine